1. Field of the Invention
The present invention relates to a mitogenic growth factor from spinal cord, its purification and uses.
2. Description of the Prior Art
Over thirty years ago Hoffman (Hoffman, R. S., Growth, 4:361-376 (1940)) and Trowell and Willmer (Trowell, O. A., and Willmer, E. N., Journal of Experimental Biology, 16:60-70 (1939)), found that water soluble extracts of brain and spinal tissue caused stimulation of cultured chicken fibroblast cells. Twenty-five years later, activity called fibroblast growth factor (FGF) was purified from the brain and pituitary gland (Gospodarowicz, D., Journal of Biological Chemistry, 250:2515-2520 (1975)). The brain factor has been isolated as two basic polypeptides of molecular weights 13,000 (FGF-1) and 11,700 (FGF-2), and the pituitary factor as a basic polypeptide of molecular weight 13,400 (Gospodarowicz et al, ADV. in Met. Disorders, 8:302-335 (1975), Gospodarowicz and Moran, Proceedings of the National Academy of Sciences, USA 71:4584-4588 (1974), Gospodarowicz et al., Journal of Biological Chemistry, 253:3736-3743 (1978), Gospodarowicz et al. "Molecular Control of Proliferation and Cytodifferentiation", Rutter, D., and Papaconstantinou, D. eds., Academy Press, New York (1978), pages 33-61, and Westall et al., Proceedings of the National Academy of Sciences USA, 75:4675-4678 (1978)).
It is believed that amphibian limbs regenerate because their neurons produce a trophic substance that enables the cells at the stump tip to divide (Singer, M., Quarterly Review of Biology, 27:169-200 (1952)). If the amputated limb is denervated early enough, then the regeneration does not occur. Both sensory and motor neurons possess the ability to cause regeneration. However, some regenerative growth can be induced if central nervous tissue homogenates are injected into a denervated limb. It has recently been shown that a basic protein is responsible for this activity (Singer et al., Journal of Experimental Zoology, 196:131-150 (1976)). It has also been found that injections of FGF caused some growth in amputated frog limbs (Gospodarowicz et al., Advances in Met. Disorders, 8:302-335 (1975)), which do not normally regenerate.
Other observations derived from amphibian limb regeneration suggest that the dividing cells might have a capacity to produce a growth self-stimulatory substance that normally resides in nervous tissue.
The availability of nervous tissue--derived purified growth factor is of interest as it would be a selective marker for nervous tissue, and would enable the promotion of growth of various cell lines including but not exclusively, transformed cell lines.